After the independent discovery of the first mGluR by Sladeczeck et al. (Nature, 317, p. 245 (1985) and by Nicoletti et al. (Jour. Neuro. Chem., 46, p. 40, (1986), the multiplicity of this class has been disclosed by expression cloning studies. Currently, eight mGluRs (and several splice variants) have been isolated and subdivided in three groups according to sequence homology, signal transduction and pharmacology: The first group includes mGluR1 and mGluR5 which are coupled to IP.sub.3 /Ca.sup.2+ signal transduction via activation of phospholipase C, whereas the members of group II, mGluR2 and mGluR3, as well as those of group III, mGluR4, mGluR6, mGluR7 and mGluR8, are negatively linked to adenylate cyclase. The conformationally restricted analogue of L-glutamic acid, (2S,2'R,3'R)-2-(2,3-dicarboxylcyclopropyl)-glycine (DCG-1/4), has been found to be a particularly interesting compound, being a potent group II mGluR agonist, which is also active as an agonist at NMDA receptor site.
The synthesis of DCG-1/4 described in the literature (Ohfune et al., International Patent Application WO 93-08158, Ohfune, et al., Bioorg. Med. Chem. Lett. 1993, 3, 15, and Ohfune et al., J. Med. Chem. 1996, 39, 407) is very long (more than 30 steps) and inefficient (only mg-quantities of the compound can be prepared). In addition, the synthesis of the radiolabeled compound is not possible using the described procedure.